title: The coagulation system and pulmonary endothelial function in acute lung injury.
abstract: Acute lung injury (ALI) is a disease marked by diffuse endothelial injury and increased capillary permeability. The coagulation system is a major participant in ALI and activation of coagulation is both a consequence and contributor to ongoing lung injury. Increased coagulation and depressed fibrinolysis result in diffuse alveolar fibrin deposition which serves to amplify pulmonary inflammation. In addition, existing evidence demonstrates a direct role for different components of coagulation on vascular endothelial barrier function. In particular, the pro-coagulant protein thrombin disrupts the endothelial actin cytoskeleton resulting in increased endothelial leak. In contrast, the anti-coagulant activated protein C (APC) confers a barrier-protective actin configuration and enhances the vascular barrier in vitro and in vivo. However, recent studies suggest a complex landscape with receptor cross-talk, temporal heterogeneity and pro-coagulant/anti-coagulant protein interactions. In this article, the major signaling pathways governing endothelial permeability in lung injury are reviewed with a particular focus on the role that endothelial proteins, such as thrombin and APC, which play on the vascular barrier function.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA. james.finigan@uhhospitals.org
authors.forename: James H
authors.initials: JH
authors.lastname: Finigan
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D011486:Protein C / Q000502:physiology / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D013925:Thromboplastin / Q000502:physiology
chemical_list: D011486:Protein C; D013925:Thromboplastin